Zinc enhances the expression of interleukin-2 and interleukin-2 receptors in HUT-78 cells by way of NF-kappaB activation.

Production of interleukin (IL)-2 is decreased in zinc-deficient human beings, and zinc is essential to IL-2-mediated T-cell activation. We used a human Th(0) malignant lymphoblastoid cell line, HUT-78, to study the effect of zinc on IL-2 production in PHA/PMA activated T-cells. In zinc-deficient cells, the gene expression of IL-2 was decreased by 50% compared with that in zinc-sufficient cells. The effect of zinc was specific and at the transcriptional level. We also showed a significant effect of zinc on the gene expression of IL-2 receptors alpha and beta. Binding of NF-kappaB (a zinc-dependent transcription factor) to DNA was decreased in zinc-deficient cells. Using transfection of expression vectors of anti-sense NF-kappaB p105 (precursor of NF-kappaB p50) in cells, we showed that a decrease in gene expression of IL-2 and IL-2 Ralpha may be partly due to decreased activation of NF-kappaB in zinc-deficient cells. Our studies demonstrate, for the first time, the role of zinc in gene expression of IL-2 and its receptors in HUT-78 cells. We also document that the binding of NF-kappaB to DNA was adversely affected, thereby decreasing the gene expression of IL-2 and IL-2 Ralpha in zinc-deficient HUT-78 cells.